Project Summary Class-V dental restorations, one of the less durable types of restorations. are fast growing in numbers because root lesions have the highest incidence in the elderly and we have a fast-growing aging population. Failure is mainly due to (1) water- and bacteria-mediated degradation of dentin encircling the restoration and (2) Class-V lesions are mainly subgingival and/or in patients with periodontal disease; ie., attachment of the surrounding periodontal tissues is compromised and more prone to biofilm accumulation and attack. Thus, there is a need for radical changes to the design of Class-V restorations. Our ultimate goal is to increase the lifetime of Class-V restorations with a disruptive technology that will incorporate nature-inspired peptides onto the surfaces of the tooth tissues and restoration to allow the latter to integrate intimately with both the soft and hard tissues surrounding it. Then, an innovative 3-tier protection system for Class-V restorations is proposed here to be developed and tested by attaining three specific aims. Specific Aim 1. First-tier Protection: Development of peptide-enhanced restored tooth surface that promotes attachment of human oral keratinocytes. Peptide 1 will be used to stimulate re-attachment of periodontal tissues, specifically the junctional epithelium, to the restored tooth. Hypothesis tested: coating the surface of dental resin composites with Peptide 1 increases epithelial keratinocyte activity in comparison to materials without such peptide. Also, based on existing waterborne latex technology, a new light-cured dimethacrylate resin coating to incorporate the peptides at the surface of the composite will be developed. Specific Aim 2. Second- and Third-tier Protection: Development of a peptide-enhanced, super-hydrophobic and antimicrobial coating for dentin. Peptide 2 will be an amphipathic and antimicrobial peptide to coat dentin. Hypothesis 1 tested: coating dentin with antimicrobial amphipathic peptides produces a super-hydrophobic dentin that is impermeable and resistant to water-mediated degradation. Effects of long exposure of the peptide-enhanced dentin to water, acid, enzymes, and bacterial challenges will be assessed. Hypothesis 2 tested: coating dentin with antimicrobial amphipathic peptides decreases both single (S. mutans) and multispecies oral biofilm growth with respect to dentin not coated with the peptides. Specific Aim 3. Increasing Mechanical Performance and Resistance to Degradation of Peptide-Enhanced Dentin-Restoration Interfaces. A super-hydrophobic and antimicrobial dentin also opens the possibility of using hydrophobic restorative materials. Hypotheses tested: a peptide-enhanced super-hydrophobic and antimicrobial dentin in combination with more hydrophobic adhesives (1) maintains the dentin-restoration bond strength, and (2) resists water- and bacteria-mediated degradation at the dentin-restoration interface. A physiologically relevant oral microbial environment will be used to challenge the restored dentin. This novel peptide-based technology for Class-V restorations will lessen elderly and periodontal patients' morbidity; improve quality of life; and reduce the associated health care costs.